Effects of Sorafenib and Arsenic Trioxide on U937 and KG-1 Cell Lines: Apoptosis or Autophagy?
Objective: Acute myeloid leukemia (AML) is a clonal disorder of hemopoietic progenitor cells. The Raf serine/threonine (Ser/Thr) protein kinase isoforms including B-Raf and RAF1, are the upstream in the MAPK cascade that play essential functions in regulating cellular proliferation and survival. A...
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doaj-73b07581768f43cb9687f0a15c9dbb632020-11-25T00:46:45ZengRoyan Institute (ACECR), TehranCell Journal2228-58062228-58142020-10-0122325326210.22074/cellj.2020.6728Effects of Sorafenib and Arsenic Trioxide on U937 and KG-1 Cell Lines: Apoptosis or Autophagy?Atousa Haghi0Mahdieh Salami1Mahnaz Mohammadi Kian2Mohsen Nikbakht3Saeed Mohammadi4Bahram Chahardouli5Shaharbano Rostami6Kianoosh Malekzadeh7Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, IranHematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, IranHematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, IranHematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, IranHematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, IranHematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, IranHematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, IranMolecular Medicine Research Center (MMRC), Hormozgan University of Medical Science (HUMS), Bandar Abbass, IranObjective: Acute myeloid leukemia (AML) is a clonal disorder of hemopoietic progenitor cells. The Raf serine/threonine (Ser/Thr) protein kinase isoforms including B-Raf and RAF1, are the upstream in the MAPK cascade that play essential functions in regulating cellular proliferation and survival. Activated autophagy-related genes have a dual role in both cell death and cell survival in cancer cells. The cytotoxic activities of arsenic trioxide (ATO) were widely assessed in many cancers. Sorafenib is known as a multikinase inhibitor which acts through suppression of Ser/Thr kinase Raf that was reported to have a key role in tumor cell signaling, proliferation, and angiogenesis. In this study, we examined the combination effect of ATO and sorafenib in AML cell lines. Materials and Methods: In this experimental study, we studied in vitro effects of ATO and sorafenib on human leukemia cell lines. The effective concentrations of compounds were determined by MTT assay in both single and combination treatments. Apoptosis was evaluated by annexin-V FITC staining. Finally, mRNA levels of apoptotic and autophagy genes were evaluated using real-time polymerase chain reaction (PCR). Results: Data demonstrated that sorafenib, ATO, and their combination significantly increase the number of apoptotic cells. We found that the combination of ATO and sorafenib significantly reduces the viability of U937 and KG-1 cells. The expression level of selective autophagy genes, ULK1 and Beclin1 decreased but LC3-II increased in U937. Conclusion: The expression levels of apoptotic and autophagy activator genes were increased in response to treatment. The crosstalk between apoptosis and autophagy is a complicated mechanism and further investigations seem to be necessary.https://celljournal.org/journal/article/abstract/6728acute myeloid leukemiaapoptosisarsenic trioxidecell proliferationsorafenib |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Atousa Haghi Mahdieh Salami Mahnaz Mohammadi Kian Mohsen Nikbakht Saeed Mohammadi Bahram Chahardouli Shaharbano Rostami Kianoosh Malekzadeh |
spellingShingle |
Atousa Haghi Mahdieh Salami Mahnaz Mohammadi Kian Mohsen Nikbakht Saeed Mohammadi Bahram Chahardouli Shaharbano Rostami Kianoosh Malekzadeh Effects of Sorafenib and Arsenic Trioxide on U937 and KG-1 Cell Lines: Apoptosis or Autophagy? Cell Journal acute myeloid leukemia apoptosis arsenic trioxide cell proliferation sorafenib |
author_facet |
Atousa Haghi Mahdieh Salami Mahnaz Mohammadi Kian Mohsen Nikbakht Saeed Mohammadi Bahram Chahardouli Shaharbano Rostami Kianoosh Malekzadeh |
author_sort |
Atousa Haghi |
title |
Effects of Sorafenib and Arsenic Trioxide on U937 and KG-1 Cell Lines: Apoptosis or Autophagy? |
title_short |
Effects of Sorafenib and Arsenic Trioxide on U937 and KG-1 Cell Lines: Apoptosis or Autophagy? |
title_full |
Effects of Sorafenib and Arsenic Trioxide on U937 and KG-1 Cell Lines: Apoptosis or Autophagy? |
title_fullStr |
Effects of Sorafenib and Arsenic Trioxide on U937 and KG-1 Cell Lines: Apoptosis or Autophagy? |
title_full_unstemmed |
Effects of Sorafenib and Arsenic Trioxide on U937 and KG-1 Cell Lines: Apoptosis or Autophagy? |
title_sort |
effects of sorafenib and arsenic trioxide on u937 and kg-1 cell lines: apoptosis or autophagy? |
publisher |
Royan Institute (ACECR), Tehran |
series |
Cell Journal |
issn |
2228-5806 2228-5814 |
publishDate |
2020-10-01 |
description |
Objective: Acute myeloid leukemia (AML) is a clonal disorder of hemopoietic progenitor cells. The Raf serine/threonine
(Ser/Thr) protein kinase isoforms including B-Raf and RAF1, are the upstream in the MAPK cascade that play essential
functions in regulating cellular proliferation and survival. Activated autophagy-related genes have a dual role in both
cell death and cell survival in cancer cells. The cytotoxic activities of arsenic trioxide (ATO) were widely assessed in
many cancers. Sorafenib is known as a multikinase inhibitor which acts through suppression of Ser/Thr kinase Raf that
was reported to have a key role in tumor cell signaling, proliferation, and angiogenesis. In this study, we examined the
combination effect of ATO and sorafenib in AML cell lines.
Materials and Methods: In this experimental study, we studied in vitro effects of ATO and sorafenib on human leukemia
cell lines. The effective concentrations of compounds were determined by MTT assay in both single and combination
treatments. Apoptosis was evaluated by annexin-V FITC staining. Finally, mRNA levels of apoptotic and autophagy
genes were evaluated using real-time polymerase chain reaction (PCR).
Results: Data demonstrated that sorafenib, ATO, and their combination significantly increase the number of apoptotic
cells. We found that the combination of ATO and sorafenib significantly reduces the viability of U937 and KG-1 cells.
The expression level of selective autophagy genes, ULK1 and Beclin1 decreased but LC3-II increased in U937.
Conclusion: The expression levels of apoptotic and autophagy activator genes were increased in response to
treatment. The crosstalk between apoptosis and autophagy is a complicated mechanism and further investigations
seem to be necessary. |
topic |
acute myeloid leukemia apoptosis arsenic trioxide cell proliferation sorafenib |
url |
https://celljournal.org/journal/article/abstract/6728 |
work_keys_str_mv |
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1725263351448076288 |